In the United States today, one in three children live in homes without the presence of their biological father. In contrast, fathers are the primary caregivers for a small but increasing number of children, as more mothers return to full-time employment. Although there is substantial evidence for the importance and unique role of fathers in shaping child social and cognitive development, few studies have directly addressed the neural underpinnings of paternal caregiving or sex differences in parenting. Rodent and more recent human research has demonstrated the importance of the neuropeptide, oxytocin, in facilitating social and parenting behaviors. The aim of this R03 application is to examine sex differences in parental brain and behavioral responses to infant cues, by measuring the effect of intranasal oxytocin on 1) fathers' neural responses using functional MRI (fMRI), and 2) interactive behavior during a free play procedure. This will be compared with data from our currently funded R01 study: Intranasal Oxytocin: A Neuropharmacological Intervention for Maternal Neglect?. Thirty first-time fathers will be enrolled, alongside their female partner and infant (from the concurrent R01 grant) in a randomized, placebo-controlled crossover study of intranasal oxytocin. FMRI brain responses to infant face cues will be measured, as well as videotaped behavioral responses of fathers during a free-play interaction procedure, the CARE-Index. It is hypothesized that fathers, compared with mothers, will show less activation of mesocorticolimbic dopamine reward circuits, including the amygdala, the ventral striatum (VS) and the ventromedial prefrontal cortex (vmPFC), when viewing their own vs. unknown infant faces during fMRI scanning. However, fathers will show greater activation of social-cognitive nigrostriatal dopamine circuits, including the dorsal striatum (DS) and the dorsolateral prefrontal cortex (dlPFC). Furthermore, it is hypothesized that intranasal oxytocin will diminish social-cognitive circuits in fathers, while enhancing affect-related brain circuitry. Finally, it is hypothesized that during the free play parent-infant interaction procedure (CARE-Index), fathers will score higher than mothers on cognitive measures (e.g. turn- taking contingencies and control) but lower on affective measures of parental sensitivity (e.g. facial and verbal expression, affection), with affective measures enhanced in fathers after intranasal oxytocin. Mothers will show a similar but less pronounced brain and behavioral response to oxytocin, reflected in a treatment x sex interaction effect. Regardless of sex, overall parental sensitivity (which incorporates both cognitive and affective measures) will be positively correlated with functional connectivity patterns between the amygdala, striatum and PFC. We anticipate that these results will help us to better understand how fathers respond to infant face cues, and elucidate sex differences in parental neuroendocrine functioning. This will provide preliminary data for an R01 application that will more fully examine paternal behavior, attachment and neuroimaging responses to intranasal oxytocin and its homologue, vasopressin.